Andres E.,University of Strasbourg |
Andres E.,Hopitaux Universitaires Of Strasbourg
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2012
Cationic host-defence antimicrobial peptides are recognised as an important component of the innate immune response in most multicellular organisms. In humans, several antimicrobial peptides have recently been recognised as key factors in the pathology of diseases such as cystic fibrosis, septic shock, atopic dermatitis and morbus Kostmann. To date, several hundred cationic antimicrobial peptides have been characterised. They are amphipathic peptides, comprising 20 to 50 amino acids, and exhibiting large structural diversity. These peptides display a broad spectrum of activity against bacterial, fungal and viral pathogens. Their mode of action is best known for cecropins and magainins, which act upon the cytoplasmic membrane of microorganisms, causing its disruption by a detergent-like activity and pore formation. In the last few years, several of these peptides or analogues (derived from magainin, protegrin, indolicidin and histatin) were in advanced clinical development, especially for localised infections (oral and cutaneous infections, pneumonias etc.). Several other molecules (rBPI, heliomicin and thanatin) are currently under development for various systemic infections (Staphylococcus sp., Aspergillus sp., Candida sp. etc.) and may represent important additions to the anti-infectious therapeutic arsenal. © Springer-Verlag 2011.
Zeisel M.B.,University of Strasbourg |
Lupberger J.,University of Strasbourg |
Fofana I.,University of Strasbourg |
Baumert T.F.,University of Strasbourg |
Baumert T.F.,Hopitaux Universitaires Of Strasbourg
Journal of Hepatology | Year: 2013
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. Furthermore, HCV-induced liver disease is a major indication of liver transplantation. In the past years, direct-acting antivirals (DAAs) targeting HCV enzymes have been developed. DAAs increase the virologic response to anti-HCV therapy but may lead to selection of drug-resistant variants and treatment failure. To date, strategies to prevent HCV infection are still lacking and antiviral therapy in immunocompromised patients, patients with advanced liver disease and HIV/HCV-co-infection remains limited. Alternative or complementary approaches addressing the limitations of current antiviral therapies are to boost the host's innate immunity or interfere with host factors required for pathogenesis. Host-targeting agents (HTAs) provide an interesting perspective for novel antiviral strategies against viral hepatitis since they have (i) a high genetic barrier to resistance, (ii) a pan-genotypic antiviral activity, and (iii) complementary mechanisms of action to DAAs and might therefore act in a synergistic manner with current standard of care or DAAs in clinical development. This review highlights HTAs against HCV infection that have potential as novel antivirals and are in preclinical or clinical development. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Piton A.,University of Strasbourg |
Piton A.,Collège de France |
Redin C.,University of Strasbourg |
Redin C.,Collège de France |
And 3 more authors.
American Journal of Human Genetics | Year: 2013
Because of the unbalanced sex ratio (1.3-1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases. © 2013 The American Society of Human Genetics.
Barth H.,Hopitaux Universitaires Of Strasbourg
World Journal of Hepatology | Year: 2015
The majority of individuals exposed to hepatitis C virus (HCV) establish a persistent infection, which is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection. Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy. The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide. Clinical trials are evaluating the best anti-viral drug combination, treatment doses and duration. The new treatments are better-tolerated and have shown success rates of more than 95%. However, the recent breakthrough in HCV treatment raises new questions and challenges, including the identification of HCVinfected patients and to link them to appropriate health care, the high pricing of HCV drugs, the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response. Finally, we still do not have a vaccine against HCV. In this concise review, we will highlight the progress made in understanding HCV infection and therapy. We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection. © The Author(s) 2015. Published by Baishideng Publishing Group Inc.
Prevalence, risk factors, maternal and fetal morbidity and mortality of intrauterine growth restriction and small-for-gestational age [Prévalence, facteurs de risque et morbi-mortalité materno-fœtale des troubles de la croissance fœtale]
Gaudineau A.,Hopitaux Universitaires Of Strasbourg
Journal de Gynecologie Obstetrique et Biologie de la Reproduction | Year: 2013
Objectives.- To assess the prevalence of fetal growth restriction (FGR) and small for gestational age (SGA) in France and other populations, the risk factors associated with SGA and its impact on fetal well-being and obstetrical outcome. Methods.- A critical review of studies identified from searches of PubMed and the Cochrane libraries using the following keywords "intra-uterine growth retardation", "intra-uterine growth restriction", "small for gestational age", " epidemiology", "risk factors", "pregnancy outcome", "maternal morbidity", "perinatal death". Results.- Studies of FGR use multiple definitions, both with respect to cutoffs for defining restricted growth as well as growth norms; however the most common definition for epidemiological research was SGA using a birthweight less than the 10th percentile. Following this definition, SGA births accounted for 8.9% of all live births in 2010 in France. Major risk factors identified in the literature were previous SGA birth (4 fold increase in risk) (LE2), diabetes and vascular diseases (5 fold) (LE3), chronic hypertension (2 fold) (LE2), preeclampsia (5 to 12 fold according to severity) (LE2), pregnancy induced hypertension (2 fold) (LE2), smoking (2-3 fold) (LE2), drug and alcohol use (2-4 fold) (LE2), maternal age over 35 (3 fold) (LE2) and ethnic origin (2-3 fold for African-American or Asian origins) (LE2). Other risk factors with adjusted odds ratios around 1.5 were primiparity (LE2), multiple pregnancy (but only starting at 30 weeks of gestation) (LE2), socioeconomic disadvantage (LE2) and body mass index (BMI < 18.5 kg/m2) (LE2) SGA is associated with a four-fold increased risk of stillbirth (LE2) as well as higher rates of cesarean and induced labor before 37 weeks. Conclusions FGR is a complication of pregnancy with adverse consequences for fetal wellbeing. Sociodemographic and clinical risk factors can help to identify pregnant women at risk for this complication. © 2013 Elsevier Masson SAS. All rights reserved.
Andres E.,Hopitaux Universitaires Of Strasbourg
Medecine des Maladies Metaboliques | Year: 2016
It has been discussed and highlighted a potential link between vitamin B12 deficiency and long-term metformin intake, especially in epidemiological studies. This link appears to be through the syndrome of food-cobalamin malabsorption. This paper develops the recent acquisitions, useful to the practitioner, regarding this syndrome. This is a newly described entity that currently holds the first place among the etiologies of cobalamin deficiency. © 2016 Elsevier Masson SAS
Cribier B.,Hopitaux Universitaires Of Strasbourg
Annales de Dermatologie et de Venereologie | Year: 2014
For a long time rosacea was thought to be mainly a vascular disorder. In the past ten years many other concepts have emerged, such as the neurovascular aspects and involvement of innate immunity. There is obviously a genetic part in rosacea, as it is much more common in people with fair skin, blue eyes and Celtic ascendance. The same persons are submitted to continental weather, with major temperature seasonal variations. Erythema and telangiectasia result from dilated superficial capillaries that have bizarre shapes, and induce constant edema of the dermis. This might be a favouring factor for Demodex colonization, which plays a major role in rosacea. Inflammation is always present, even in erythematotelangiectatic subtypes. It involves innate immunity, in response to environmental factors, like Demodex and its own biotope, resulting in overproduction of LL37, a pro-inflammatory peptide able to induce skin inflammation in an animal model, trough activation of inflammatory cells. Tool like receptors are involved in the activation of innate immunity. Demodex is the cause of ganulomas seen in papulopustular rosacea, but it is also always present in the erythematotelangiectatic subtypoe. Colonization by Demodex is nevertheless not decreased with conventional treatments of rosacea, like tetracyclins and metronizaole. This might be due to induction of inflamation by bacteria hosted by Demodex, like Bacillus oleronius, and dozens of bacteria that are being investigated. Finaly, rhinophyma is linked to both vascular changes and activation of fibrosis, involving TGF beta. © 2014 Elsevier Masson SAS. All rights reserved.
Schultz P.,Hopitaux Universitaires Of Strasbourg
European Annals of Otorhinolaryngology, Head and Neck Diseases | Year: 2011
Ninety percent of vocal fold cancers take the form of squamous cell carcinoma. Since the 1980s, incidence in France has been constantly falling in males while increasing in females. The main risk factor is smoking, alcohol being less implicated than in other laryngeal or extralaryngeal locations. Vocal fold squamous cell carcinoma generally develops on healthy mucosa, although primary precancerous lesions such as leukoplakia or papillomatous keratosis are also frequent. The tumor usually originates in the non-lymphophilic mucosal free edge of the vocal fold then invades the various anatomic subunits of the larynx, acquiring lymph-node metastatic potential. Dysphonia is the first presenting symptom, initially caused by defective mucosal vibration and then by impaired mobility and finally fixation of the vocal fold. Extension, risk factor and pretreatment assessments are as in other upper-aerodigestive-tract cancer locations. The possibilities of laryngoscopic exposure and the tumor limits, however, need to be precisely determined if transoral resection is to be considered. For small tumors, surgery or exclusive radiation therapy can be suggested to the patient as part of an individual treatment plan, each having its advantages and drawbacks. Cutting-edge teams report 5-year local control rates of 85-95% in T1-class tumor and 60-90% in T2. Whatever the treatment option, smoking cessation, close surveillance and cardiovascular prevention enable screening of other oncologic locations and limit onset of the other pathologies implicated in most deaths. © 2011 Elsevier Masson SAS. All rights reserved.
Durand E.,Hopitaux Universitaires Of Strasbourg
Seminars in Nuclear Medicine | Year: 2014
Nuclear medicine and MRI provide information about renal perfusion, function (glomerular filtration rate), and drainage. Some tracers that are used in nuclear medicine (technetium-diethylene triamine pentaacetic acid ([ 99mTc-DTPA] and 51chromium-EDTA) and some contrast media (CM) that are used for MRI (gadolinium-DTPA for instance) share the same pharmacokinetic properties, though, detection techniques are different (low-spatial resolution 2-dimensional projection with a good concentration-to-signal linearity for nuclear medicine and high-resolution 3-dimensional localization with nonlinear behavior for MRI). Thus, though based on the same principles, the methods are not the same and they provide somewhat different information. Many MRI perfusion studies have been conducted; some of them were compared with nuclear medicine with no good agreement. Phase contrast can reliably assess global renal blood flow but not perfusion at a tissular level. Arterial spin labeling has not proven to be a reliable tool to measure renal perfusion. Techniques using CM theoretically can assess perfusion at the tissular level, but they have not proven to be precise. To assess renal function, many models have been proposed. Some MRI techniques using CM, both semiquantitative (Patlak) and quantitative, have shown ability to roughly assess relative function. Some quantitative methods (Annet's and Lee's methods) have even showed that they could roughly estimate absolute renal function, with better results than estimated glomerular filtration rate. Quantification of drainage has not been much studied using MRI. © 2014 Elsevier Inc.
Roy C.,Hopitaux Universitaires Of Strasbourg
Diagnostic and Interventional Imaging | Year: 2012
Bladder cancer occurs frequently and is serious. Although ultrasound and CT examination are essential, magnetic resonance imaging is more effective for staging large tumours and in atypical cases, in particular submucosal lesions. CT and MRI are equally effective in examining the lymph nodes. The examination technique is simple. The prospects for using MRI, in particular with diffusion imaging, are being evaluated. © 2012 Published by Elsevier Masson SAS on behalf of the Éditions françaises de radiologie.